A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression chang...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/17915 |
| _version_ | 1818019787649843200 |
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| author | Nathan G Skene Marcia Roy Seth GN Grant |
| author_facet | Nathan G Skene Marcia Roy Seth GN Grant |
| author_sort | Nathan G Skene |
| collection | DOAJ |
| description | The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia. |
| first_indexed | 2024-04-14T07:55:58Z |
| format | Article |
| id | doaj.art-abb53584a758407eb234ffdf29f59d44 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:55:58Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-abb53584a758407eb234ffdf29f59d442022-12-22T02:05:03ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.17915A genomic lifespan program that reorganises the young adult brain is targeted in schizophreniaNathan G Skene0https://orcid.org/0000-0002-6807-3180Marcia Roy1https://orcid.org/0000-0002-4088-3958Seth GN Grant2https://orcid.org/0000-0001-8732-8735Genes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United KingdomGenes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United KingdomGenes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United KingdomThe genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.https://elifesciences.org/articles/17915transcriptomicsSchizophreniapost-mortem |
| spellingShingle | Nathan G Skene Marcia Roy Seth GN Grant A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia eLife transcriptomics Schizophrenia post-mortem |
| title | A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| title_full | A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| title_fullStr | A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| title_full_unstemmed | A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| title_short | A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| title_sort | genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia |
| topic | transcriptomics Schizophrenia post-mortem |
| url | https://elifesciences.org/articles/17915 |
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